chr7-2355129-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001037283.2(EIF3B):​c.208C>T​(p.Pro70Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,403,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

EIF3B
NM_001037283.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.326
Variant links:
Genes affected
EIF3B (HGNC:3280): (eukaryotic translation initiation factor 3 subunit B) Enables RNA binding activity. Contributes to translation initiation factor activity. Involved in several processes, including IRES-dependent viral translational initiation; translational initiation; and viral translational termination-reinitiation. Located in extracellular exosome. Part of eukaryotic translation initiation factor 3 complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.06706062).
BS2
High AC in GnomAdExome4 at 31 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EIF3BNM_001037283.2 linkc.208C>T p.Pro70Ser missense_variant Exon 1 of 19 ENST00000360876.9 NP_001032360.1 P55884-1A0A024R821

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EIF3BENST00000360876.9 linkc.208C>T p.Pro70Ser missense_variant Exon 1 of 19 1 NM_001037283.2 ENSP00000354125.4 P55884-1
EIF3BENST00000397011.2 linkc.208C>T p.Pro70Ser missense_variant Exon 1 of 19 1 ENSP00000380206.2 P55884-1
EIF3BENST00000413917.5 linkc.195+13C>T intron_variant Intron 1 of 6 2 ENSP00000407785.1 C9JZG1
EIF3BENST00000431643.5 linkc.-504-105C>T intron_variant Intron 1 of 7 5 ENSP00000408062.1 C9JQN7

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151478
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000657
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000248
AC:
31
AN:
1251618
Hom.:
0
Cov.:
36
AF XY:
0.0000179
AC XY:
11
AN XY:
613694
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000163
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000265
Gnomad4 OTH exome
AF:
0.0000581
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151478
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
73978
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000657
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000148
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 29, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.208C>T (p.P70S) alteration is located in exon 1 (coding exon 1) of the EIF3B gene. This alteration results from a C to T substitution at nucleotide position 208, causing the proline (P) at amino acid position 70 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
11
DANN
Uncertain
0.99
DEOGEN2
Benign
0.022
T;T
Eigen
Benign
-0.89
Eigen_PC
Benign
-0.93
FATHMM_MKL
Benign
0.0056
N
LIST_S2
Benign
0.47
.;T
M_CAP
Uncertain
0.19
D
MetaRNN
Benign
0.067
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;N
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.10
N;N
REVEL
Benign
0.033
Sift
Benign
0.042
D;D
Sift4G
Benign
0.15
T;T
Polyphen
0.0
B;B
Vest4
0.064
MutPred
0.27
Gain of phosphorylation at P70 (P = 0.0017);Gain of phosphorylation at P70 (P = 0.0017);
MVP
0.17
MPC
0.38
ClinPred
0.055
T
GERP RS
2.3
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
3.5
Varity_R
0.040
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1228059961; hg19: chr7-2394764; API